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A Reagent for Amine-Directed Conjugation to IgG1 Antibodies

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Functionalized antibodies are an indispensable resource for diagnosis, therapy and as a research tool for chemical biology. However, simpler and better methodologies are often required to improve the labeling of antibodies in terms of selectivity and scalability, in particular for the production of antibody drug conjugates. Herein, we report the development of an easily available chemical reagent that allows site-directed labeling of native human IgG1 antibodies. The labeling procedure has low time demand, and only one reagent is needed. The salicylaldehyde moiety of the reagent reacts with surface exposed lysine residues to transiently form an iminium ion, and this positions a semi-reactive ester into proximity of a second lysine residue that reacts with the ester to form an amide. Interestingly, it appears that the formation of the iminium ion also has a significant activating effect of the ester. We show that the reagent can effectively be used to conjugate functionalities of interest to human IgG1 antibodies in good yield and conversion. Moreover, the reagent allows for high control of number of labels per antibody. We use flow cytometry and bio-layer interferometry to confirm that the labeled antibodies retain antigen binding.

TidsskriftAngewandte Chemie International Edition
Sider (fra-til)6539-6544
Antal sider6
StatusUdgivet - mar. 2021

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